1. Field of the Invention
The present invention relates to a compound which exhibits antitumor activity, a method for isolating the compound from a red alga, and methods for using the compound. More specifically, the present invention relates to: isolation and identification of a new chemical compound, and of medically useful compositions containing the same. The compound of the present invention exhibits advantageous pharmacological, toxicological or antitumor properties, such as, for example, killing or inhibiting the growth of human tumors.
2. Description of Related Art
Since the mid-1970's the Rhodophyta (red algae) have been known to produce halogenated monoterpenes [Stallard, M. O., et al: Comp. Biochem. Physiol. B, 49: 25-35, 1974]. Although scores of acyclic, monocyclic and bicyclic halogenated monoterpenes have been identified [Sims, J. J., et al: In Marine Natural Products, Chemical and Biological Perspectives, (Scheuer, P. J., ed.), New York: Academic Press, 1978, pp. 297-378], this class of compounds has been confined to the genera Plocamium and Chondrococcus. The structure elucidation of these compounds has not been a simple task. The relatively volatile monoterpenes tend to decompose under electron-impact ionization mass spectrometry (EI-MS) conditions and acquisition of molecular weight and formula information has often been difficult. Correct placement of chlorine and bromine substituents has not proven to be straightforward, as NMR chemical shift arguments are clouded by the cumulative effects of multiple substituents on the C.sub.10 skeleton.
The compound of the present invention is 6(R)-bromo-3(S)-bromomethyl-7-methyl-2,3,7-trichloro-1-octene. A compound proposed to have the same structure as the compound of the present invention was reported previously by Burreson et al., [Burreson, B. J., et al: Chemistry Lett., 1111-1114, 1975.] as an unresolved component in a mixture of monoterpenes from Chondrococcus hornemannii; however, the material was only partially characterized. Neither a proof of the structure, nor the absolute stereochemistry (there are two chiral centers, carbon atoms 3 and 6, and thus four possible diasteromers), nor a method of isolating the compound of the present invention in substantially pure form has previously been reported in the literature.
Other carbocyclic halomonoterpenes from Rhodophyta reportedly have shown general cytotoxicity in brine shrimp assays [Konig, G. M., et al: J. Nat. Prod. 53: 1615-1618, 1990] and in vitro inhibition of murine leukemia [Gonzales, A. G., et al: Planta Med. 44: 44-46, 1982] or other [Kusumi, T., et al: J. Org. Chem. 52: 4597-4600, 1987] cell lines. However, the novel profiles of selective antitumor activity of the compound of the present invention that can be demonstrated in the U.S. National Cancer Institute's new disease-oriented primary screen, which predicts antitumor activity against human solid tumors, has not previously been reported for any halomonoterpene in the literature. Neither the specific compound of the invention nor pharmaceutical compositions of the compound nor methods of using the compound or compositions thereof for treatment of cancer have been heretofore described.